Sulfonium compounds



Patented Mar. 11, 1947 UNITED STATES PATENT OFFICE SULFONIUM COLIPOUNDS Edgar G. Britten and John N. Hansen, Midland,

Mich., assignors to The Dow Chemical Company, Midland, Mich., a corporation of Michig an No Drawing. Application December 26, 1944,

Serial No. 569,933

Some are objectionable because of odor, instabil- 1 ity, toxicity, or tendencies to irritate the skin of humans when contacted therewith. Others have solubility characteristics which make their use in aqueous compositions impractical, except as they may be employed in combination with excessive amounts of Wetting, dispersing, or solubilizing agents. Still other compounds have relatively high vapor pressures, whereby they volatilize from compositions in which they are employed or out of contact with the surfaces to which they are applied, so that extended protection against microorganisms is not obtained. I

The new compounds of the present invention are characterized by a fortunate combination of properties whereby they are adequately soluble in water, of high germicidal and bactericidal effectiveness, substantially odorless, of low volatility, stable, and relatively non-irritating to the skin of humans and higher animals. These compounds have been found valuable for the control of micro-organisms.

One .method for the preparation of the compounds of the present invention includes condensing a phenol with a suitable dihalo-polyalkylene ether in the presence of sodium hydroxide to form a compound of the formula wherein R is an aromatic radical of the benzene series, Z represents halogen, and m and n are each an integer from 2 to 4, inclusive. Such product is then reacted with a suitable sodium mercaptide to form a sulfide of the formula wherein R, m and n have the values set forth above, and-R. represents alkyl or aralkyl. Such sulfide is then reacted with a suitable alkyl ester and preferably an ester of an inorganic acid to give a sulfoniurn compound of the formula wherein R represents an aromatic radical of the benzene series, B. represents alkyl or aralkyl, m and n are each an integer from 2 to 4, inclusive, and X represents a mono-basic acid radical. The expression alkyl refers particularly to radicals containing from 1 to 18 carbon atoms, inclusive. The expression of the benzene series as herein employed in the definition of the symbol Rf refers to mononuclear aromatic structures characterized by the phenyl ring and homologues and analogues thereof in distinctionto heterocyclic Here, Y represents hydrocarbon and particularly aralkyl, cyclohexyl, phenyl, or alkyl. These compounds are particularly suited for use in bactericidal and antiseptic compositions. A further embodiment resides in those compounds in which R represents the structure In this formula, w is an integer from 1 to 5; inclusive. These compounds are good as fungicides. Other preferred features of the generic structure, as set forth above, include compounds in which the polyalkylene ether grouping consists of a plurality of ethoxy radicals and preferably 2.

and in which one of the hydrocarbon radicals attached to sulfur is methyl.

. The following examples illustrate the invention, but are not to be construed as limiting.

Example 1 20 grams (0.5 mole) of sodium hydroxide was dissolvedin a mixture of 35 milliliters of water and 400 milliliters of ethanol. 45 grams (0.5 mole) of normalbutyl mercaptan and 138 grams (0.5 mole) of beta-chloro-beta-(2-xenoxy)-diethyl ether were added to the caustic solution and the mixture heated to boiling temperature'and under reflux for 7 hours. The resulting product was as an oil.

diluted with water to dissolve the sodium chloride formed and thereafter extracted with benzene. The benzene extract was washed successively with dilute aqueous sodium hydroxide and water and the benzene separated by distillation under reduced pressure.- The residue consisted of normalbutyl beta- [beta- (2-xenoxy) -ethoxyl -ethyl sulfide as a straw-colored oil.

33 grams (0.1 mole) of the sulfide as described above and 12.6 grams (0.1 mole) of dimethyl sulfate were mixed together and heated at 72 C. for 42 hours. dissolved in a small amount of absolute ethanol and thereafter diluted with diethyl ether to throw out of solution the sulfonium reaction products This operation was repeated several times, the oil separated, and the last tracesof solvent removed by warming the product under reduced pressure. Normalbutyl methyl beta- [beta- (2-xenoxy) -ethoxy] -ethyl sulfonium methosulfate was thereby obtained in the form of a clear viscous oil. This compound is readily soluble in ethanol, water, and benzene, and relatively insoluble in diethyl ether.

Example 2 In a similar manner normalbutyl mercaptan and beta- [beta- (2.3.4.6 tetrachloro phenoxy) ethoxy'l-ethyl chloride were reacted together in the presence of sodium hydroxide to obtain normalbutyl beta-[beta-(2.3.4.6-tetrachloro phenoxy) -ethoxy] -ethyl sulfide. 78.4 grams (0.2 mole) of this sulfide and 25.2 grams (0.2 mole) of dimethyl sulfate were mixed together and heated at 70 C. for approximately 18 hours. The crude reaction product was dissolved in a small amount of absolute ethanol and thereafter thrown out of solution as an oil by dilution with diethyl ether. The oily product was separated by decantation, and the procedure repeated. The ultimate residue was warmed under reduced pressure to remove residual solvent. The product from this operation consisted of normalbutyl methyl beta- [beta (2.3.4.6-tetrachloro phenoxy)-ethoxy]- ethyl sulfonium methosulfate as a light viscous oil readily soluble in water, ethanol, and ben.. acne, and insoluble in diethyl ether.

Example 3 Equimolecular proportions of .beta-[beta-(4- cyclohexyl-phenoxy) -ethoxyl-ethyl chloride and normalbutyl mercaptan'were reacted together in the presence of an equivalent proportion of sodium hydroxide dissolved in 90 per cent ethanol substantially as described in Example 1. 50.4 grams (0.15 mole) of the resulting normalbutyl beta v[beta (4 cyclohexyl-phenoxy) -ethoxy]- ethyl sulfide and 18.9 grams (0.15 mole) of dimethyl sulfate were mixed together and heated at 70 C. for 21 hours. The usual purification steps of dissolving in absolute alcohol and precipitation with diethyl ether were followed and. the ultimate insoluble residue warmed under reduced pressure to remove traces of solvent. The prodnot from this treatment consisted of 53 grams of normalbutyl methyl beta-[beta-(l-cyclohexyl phenoxy) -ethoxyl-ethyl sulfonlum methosulfate as a viscous straw-colored liquid completely miscible with water, soluble in absolute ethanol, and insoluble in diethyl ether.

Example 4 I 90grams (1 mole) of normalbutyl merca'ptan; 40 grams (1 mole) of sodium hydroxide, 380.5 grams of beta-Ebeta- (X-aIphaphenyIethyI-Z-Xen- The reaction mixture was thenxy)-ethoxy]-ethyl chloride, 75 milliliters of water, and 1 liter of ethanol were mixed together and heated to boiling temperature and under refiux for 22 hours. The major proportion of the ethanol was then recovered by fractional distillation under reduced pressure and the residue from the distillation operation diluted with water to dissolve precipitated sodium chloride. The mixture was then extracted with benzene, and the benzene distilled oil to recover as a residue 421 grams of normalbutyl beta-[beta-(x-alphaphenylethyl-Z-xenuxy)-ethoxyl-ethyl sulfide as a straw-colored viscous oil.

86.8 grams (0.2 mole) of this sulfide and 25.2 grams (0.2 mole) of dimethyl sulfate were reacted together and heated at 70 C. for 21 hours. The crude reaction product was dissolved in a small amount of ethanol and thereafter diluted with diethyl ether to throw out of solution the sulfonium reaction product. This oily product was separated by decantation, washed with, diethyl ether, and warmed under reduced pressure to remove traces of solvent. From these operations there was obtained 103 grams of normalbutyl methyl beta-[beta-(x-alphaphenylethyl-2- xenoxy)-ethoxy]ethyl sulfonium methosulfate as a straw-colored viscous oil completely soluble in water and ethanol, and relatively insoluble in diethyl ether.

Example 5 43.4 grams (0.1 mole) of the sulfide as described in Example 4 and 18.6 grams (01 mole) of methyl-paratoluene-sulfonate were mixed together and heated at 98 C. for 40 hours. The resulting crude product was dissolved in ethyl alcohol and thereafter precipitated as a viscous oil by the addition of a small amount of water to the alcohol mixture. This oily product was dried to obtain a substantially theoretical yield of normalbutyl methyl beta-[beta-(x-alphaphenylethyl-2- xenoxy)-ethoxyl-ethy1 sulfonium paratoluenesulfonate as a viscous liquid soluble in ethanol, and diiiicultl-y soluble in water and diethyl ether.

Example 6 43.4 grams (0.1 mole) of'the sulfide described in Example 4 and 14.2 grams (0.1 mole) of methyl iodide were mixed together and allowed to stand under autogenous pressure at 25-30 C. for 46 hours. The resulting crude product was purified by dissolving in ethanol. and precipitation with diethyl ether in the. usual manner to obtain normalbutyl methyl beta-[beta-(x-alphaphenylethyl-2-xenoxy) -ethoxy] -ethyl sulfonium iodide as a very viscous liquid soluble in ethanol and relatively insoluble in diethyl ether and water.

Example 7 310 grams (1.0 mole) of beta-=[beta-(monochloro-2-xenoxy) -ethoxyl-ethy1 chloride, grams (1 mole) of normalbutyl mercaptan, 40 grams (1 mole) of sodiumhydroxide, 75 milliliters of water, and 800 milliliters of ethanol were mixed and reacted together substantially as described in Example 1 for 12 hours at the boiling temperature of the mixture and under reflux. As the product from this reaction there was obtained 360 grams of normalbutyl beta-[beta-(monochloro-Z-xenoxy)-ethoxyl-ethyl sulfide as a light viscous oil, very soluble in benzene, and difiicultly soluble in water.

360 grams (0.998 mole) of this sulfide and 126 grams (1.0 mole) of dimethyl sulfate were mixed together. Considerable heat of reaction "was evolved and the mixture was allowed'tostand at room temperature for 18 hours. The resulting crude product was warmed on a steam bath, dissolved in approximately 150 milliliters of abso'-' lute alcohol, and cooled. The solution was then diluted with diethyl ether to throw out normal:- butyl methyl beta-[beta-(monochloro-Z-xen: oxy) -ethoxyl-ethyl sulfonium methosulfate as a viscous light colored oil. This purification step with ethanol and ether was repeated several times and the ultimate residue warmed under reduced pressure to remove traces of solvent. The desired sulfonium compound was thereby obtained as a relatively viscous oil, readily soluble in water, ethanol, and benzene, and difficultly soluble in diethyl ether.

Example 8 49.15 grams (0.1 mole) of the sulfonium methosulfate salt as described in the preceding example was dissolved in 200 milliliters of water. A solution of 16 grams (0.1 mole) of sodium salicylate in '75 milliliters of water was added to the solution with stirring. A clear straw-colored oil separated from solution and was recovered by extraction with ethylene chloride. The solvent was evaporated off to obtain 51 grams of normalbutyl methyl beta-[beta-(monochloro-2- xenoxy)-ethoxyl -ethy1 sulfonium salicylate as a viscous oil having a strong odor of Wintergreen, soluble in ethanol, ethyl ether, and benzene, and relatively insoluble in water, petroleum ether, and carbon tetrachloride.

Example 9 27.6 grams of alphaphenylethyl mercaptan was added portion-wise and with stirring to a solution of 8.34 grams of sodium hydroxide in milliliters of water. A white solid formed. This product was added along with 76.1 grams of beta [beta (x-alaphaphenylethyl-2-xenoxy)- ethoxy] -e thyl chloride to 200 milliliters of 95 per cent ethanol and the mixture heated to boiling temperature and under reflux for 24 hours. The resulting crude reaction product was cooled, diluted with water, and extracted with benzene. The benzene extract was successively washed with dilute aqueous sodium hydroxide-and water and the benzene evaporated off under reduced pressure. alphaphenylethyl beta-[beta alphaphenylethyl- 2-xenoxy)-ethoxyl-ethyl sulfide as a strawcolored oil.

45 grams of the foregoing sulfide and 11.8 grams of dimethyl sulfate were mixed together and heated at 65 C. for 55.minutes. The reaction product was then dissolved in absolute ethanol and the sulfonium salt thrown out of solution by dilution with diethyl ether. The mixed solvents were decanted off and the oily residue washed with diethyl ether and warmed under reduced pressure to remove traces of solvent. The product from the reaction consisted of 38 grams of methyl alphaphenylethyl beta- [beta (x-alphaphenylethyl-2-xenoxy) -ethoxy]- ethyl sulfonium methosulfate soluble in ethanol and insoluble in diethyl ether. The product was completely soluble in water to give a clear foaming solution.

, Example 10 der refiux for 24 hours.

The residue consisted of 9'7 grams of phenoxy)'- ethoxy] iethyl' sulfide as ayellow .oil; 38.4 grams (0.1 mole) of this sulfide and 12.6 grams (0.1 mole) of dimethyl sulfate were mixed together and heated at C. for 40 minutes. The crude reaction product was dissolved in 20 milliliters of absolute alcohol and thereafter thrown out of solution by dilution with 400 mill-. liters of diethyl ether. The mixed solvents were decanted off and the residue washed with ether and dried under reduced pressure. As a residue there was obtained 30 grams of methyl alphapheny'l-ethyl beta [beta '(4-cyclohexyl-phen oxy)-ethox'y]-ethyl sulfonium methosulfate" as a clear viscous oil dissolving in water to give a clear, foamy, and slightly viscous solution. j

Example 11 Example 12 0.2 molar quantities of sodium hydroxide and beta (x alphaphenylethyl-2-xenoxy)-beta'- chloro-diethyl ether were reacted with a keryl mercaptan obtained as a commercial product prepared from kerosene and embodying an average alkyl group of C13. (This keryl mercaptan contained 11.512.5 per cent sulfur and had a boiling range of -180 C. at 5 millimeters pres-' sure.) The reaction was carried out in per cent ethanol and at boiling temperature and un- The usual dilution of the crude reaction mixture with water and ex-' traction with benzene was carried out. As the product of reaction there was obtained grams of keryl beta-[beta-(x-alphaphenylethyl 2-xenoxy) -ethoxyll-ethyl sulfide as a viscous amber oil of not unpleasant odor.

56 grams (0.1 mole) of the above sulfide product and 15.1 grams (0.12 mole) of dimethyl sulfate were mixed and heated at 65 C. for 19 hours. After the usual purification of the crude oily product with ethanol and ether, there was obtained 43 grams of keryl methyl beta-[beta- (x'-alpha phenyl-ethyl 2-xenoxy) -ethoxyl -ethyl sulfonium methosulfate as a dark viscous oil com- 0 pletely soluble in water, soluble in ethanol, and

insoluble in diethyl ether.

- I Example 13 Equimolecular proportions of a commercial mixed amyl mercaptanproduct and beta-(2.3.4.6- tetrachloro-phenoxy) -beta'-chloro-diet-hel ether were reacted together in alcohol and water and in the presence of sodium hydroxide substantially 70 as described in the previous examples. The product was purified in the usual manner to obtain 398 grams of amyl beta-[beta-(2.3.4.6-tetrachloro-phenoxy) -ethoxyl-ethyl sulfide as a yellow viscous liquid.- 203 grams of this sulfide p oduct nd. .3 rams ofdim y sul at ere mixed together and heated .for .16 .hours on .a

steam bath. The resulting product E-con'sisted essentially :of amyl methyl kb.eta-[beta-(2.3.4.6- tetrachloro-phenoxy)-ethoxyJ -tethyl :sulfonium methosulfate as a clear blOWIlSSYllllJ, rather viscous at reduced temperatures, and completely soluble .in water.

' Example I114 025 molar proportion of sodium hydroxide, lauryl mercaptan and beta-(4-cyclohexyl-phenoxy) -beta"-chloro-diethyl ether'were reacted together in a mixture of 18 milliliters of water and 200 milliliters of 95per cent ethanol. The usual steps of heating under reflux, extraction and washing were carried out to obtain 112 grams of lauryl beta-[beta-.(4-cyclohexyl-phenoxy) ethoxyl-ethyl sulfide as a straw-colored oil. 44.8 grams (0.1 mole) of this sulfide and 12.6 grams (0.1 mole) of dimethyl sulfate were heated together at 65 C. for 18 hours. The resulting crude product was dissolved in'diethyl ether and "thereafter thrown out of solution by dilution with an excess of petroleum ether. The mixed solvents were decanted and the 'oily residue washed twice with petroleum ether and warmed under reduced pressure to drive off traces of solvent. As the product of reaction there was obtained 50 grams of 'lauryl methyl beta-[beta-'(4-cyclohexyl-phenoxy) -ethoxyl -ethyl sulfonium methosulfate as a yellow-brown pasty material soluble in water.

Example .15

951 grams of beta-(x-alphaphenylethyl-Z- xenoxy) -diethyl ether and 160 grams of a freshly distilled commercial mercaptan mixture containing 26 per cent by weight of methyl mercaptan, 59 per cent by weight of ethyl .mercaptan, and 7 per cent by weight of butyl mercaptan were re acted together in the presence of 2.0 moles of sodium hydroxide dissolved in 1'75 milliliters of water and 2,000 milliliters of 95 per cent ethanol. The reaction was carried out bypassing the mercaptan mixture into the liquid caustic solution at C. and overa period of minutes, and thereafter adding the diethyl ether compound. The mixture was allowed to stand overnight. The product was then heated to boiling temperature under reflux and with-stirring for 24 hours. The alcohol was recovered by fractional distillation and the residue washed with water and extracted with carbon tetrachloride. The carbon tetrachloride extract was washed with water and the solvent distilled off under reducedpressure to obtain a mixed sulfide product as a clear winecolored syrup in the amount of 9'70 grams. This product contained 7.7 per cent by weight of sulfur.

206.5 grams .of the sulfidev product as obtained above and 63 "grams of dimethyl sulfate were mixed together and heated at-65 C. .for 2 hours. The reaction product was -iound to be a mixed sulfonium methosulfate as a viscous oil completely soluble in Water.

Example 16 Other sulfonlum salt compounds which may be prepared substantially as described'in the foregoing examples include the following:

Ethyl methyl betabeta-(beta-'(l-xenoxy)- ethoxy) -ethoxy] -ethyl sulionium ethylsulfate by reacting methyl beta- [beta- (betal-xenoxy) ethoxy)-ethoxyl-ethyl sulfide with diethyl sulfate.

'Dimethyl betal-beta "(beta- (betaplhenoxyethoiwl-ethoiw) -"ethoxy'l--ethyl siilionium bromide by reacting together methyl beta-[beta- (beta (beta-phenoxy-ethoxy) -ethoxy) -ethoxy]- ethyl sulfide and methyl bromide.

Octadecyl propyl gamma-[gamma-(4-chloro- 5 phenoxy) -propoxy] -propyl sulfonium propyl sulfate by reacting octadecyl .gamma-[gamma-(lchlorophenoxy)-'-propoxy] -propyl sulfide with dipropyl sulfate.

Tertiarybutyl benzyl gamma-[gamma-(gamma- (gamma pentachlorop-henoxy propoxy) propoxy) -propoxy] -propyl sulfonium chloride by reacting benzyl gamma [gamma (gamma (gamma pentachlorophenoxy propoxy) propoxy-propoxyl-propyl sulfide with tertiarybutyl chloride.

Isopropyl secondaryoctyl delta-[delta-(Z-cyclohexyl-4-chlorophenoxy) -.normalbutoxyl -normalbutyl sulfonium iodide by reacting secondaryoctyl delta [delta (2-cyclohexyl-4-chlorophenoxy)-normalbutoxy] normalbutyl sulfide with isopropyl iodide.

Betaphenylethyl octadecyl delta-[delta-(delta- (delta (2.5- dichlorophenoxy) normalbutoxy) normalbutoxy) -normalbutoxy] -normalbutyl sulfonium bromide by reacting l'oetaphenylethyl delta [delta (delta (delta- (2.5 dichlorophenoxy) normalbutoxy norma'lbutoxy) -normalbutoxyl-norma'lbutyl sulfide with octadecyl bromide.

Normalbutyl methyl beta-[beta-(2.4-dinitro- 6 methylphenoxy) ethoxy] ethyl sulfonium methosulfate by reacting dimethyl sulfate with normalbutyl beta-[bta-(ZA-dinitro 6 methylphenoxy) -ethoxy] -ethyl sulfide.

Normalpropyl ethyl .beta- [betabeta- (l-secondary-lbutyl-phenoxy) -ethoxy) ethoxy] ethyl sulfonium bromide by'reacting ethyl bromide with normalpropyl beta-'[beta-(beta (4 secondarybutyl-phenoxy) -ethoxy) -ethoxyl -ethyl sulfide.

Secondarybutyl ethyl beta-[beta- (2-methyl-4- tertiaryoctyl-phenoxy) -ethoxy] -ethyl sulfonium chloride by reacting secondarybutyl beta-[beta- (2 methyl-i -tertiaryoctyl phenoxy) ethoxylethyl sulfide with ethyl chloride.

Normalhexyl methyl beta-[beta-(2.4.6-tribromophenoxy) -ethoxyl-ethyl sulfom'um methosulfate 'by reacting normalhexyl beta- [beta-(2.4.6- tribromophenoxy) -ethoxyl-ethyl sulfide with dimethyl sulfate.

Isopropyl normalbutyl gamma gamma-(4- normaloctylphenoxy) propoxy] -propyl sulfonium bromide by reacting isopropyl gamma-[gamma- (4-normaloctyl-phenoxy) -propoxyl-'propyl sulfide with normalbutyl bromide.

'Normalpropy'l methyl beta- [beta-(l-benzylphenoxy) -ethoxyl-ethyl sulfonium bromide by reacting methyl 'beta- [beta- (4-benzyl-p'henoxy) 4 ethoxyl-ethyl sulfide with normalbutyl bromide.

Normalbutyl methyl beta-[beta-(4-iodo-phe- 60 noxy)-ethoxy'] -ethyl sulfonium methosulfate by reacting normalbutyl beta-[beta-(-iodo -phenoxy)-ethoxy]-ethyl sulfide with dimethyl sulfate.

We claim:

1. A sulfonium compoundhaving the formula CH8 @o-omoHe-oomcmemk 1 01.. 1':

wherein w represents an integer not greater than 5, and 'Xrepresents a mono-basic acid radical.

'2. Normalbutyl methyl beta- [beta-(2.3.4.6- tetrachlorophenoxy) ethoxyl ethyl 'sulfonium 735 methosulfate.

3. Normalbutyl methyl beta-[beta-(2.4.5-trichlorophenoxy) -ethoxy] -ethyl sulfonium methosulfate.

EDGAR C. BRIITON. JOHN N. HANSEN.

REFERENCES CITED The following references are of record in the file of this patent:

UNITED STATES PATENTS Number Name Date 2,204,967 Van Peski June 18, 1940 2,107,366 Bruson Feb. 8, 1938 2,121,832 Pigg'oti; June 28, 1938 OTHER REFERENCES Renshaw, Jour. Am. Chem. Soc., vol. 55, pp. 4951 to 4953 (1933). 

